Leishmania major infections in genetically susceptible and resistant mice will be used as models for the study of immunity to cutaeous leishmaniasis. Non-healing infections in susceptible (BALB/c) mice are characterized by the development of both T suppressor cells and prostaglandin-secreting suppressor macrophages. The underlying causes for induction of these suppressor cells in susceptible, but not resistant, mice has yet to be determined. Efforts will be made to characterize differences in macrophage antigen presenting capacity between healing and non-healing strains and to evaluate macrophage functional abnormalities as the basis for genetic susceptibility to L. major. Studies will concentrate on how infection might alter the production of prostaglandins or the expression of I region gene products (Ia antigens) by macrophages. The induction and maintenance of Ia expression by lymphokines will be assessed in vitro and correlated with in vivo Ia expression by cells from infected mice. Attempts will also be made to determine if prostaglandins play a major role in modulation of Ia expression and the induction of T suppressor cells. Finally, attempts will be made to modulate Ia expression by leishmanial-antigen presenting cells and test the ability of these cells to immunize mice against infection.